Nuclear imaging techniques for cardiac amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis is a condition marked by the misfolding of precursor proteins into insoluble amyloid fibrils, leading to restrictive cardiomyopathy and heart failure symptoms. This review discusses advancements in nuclear imaging techniques that enhance the diagnosis and guide the management of cardiac amyloidosis, addressing the critical need for early and accurate detection in clinical practice. RECENT FINDINGS: Recent studies and guidelines emphasizes the pivotal role of nuclear imaging techniques in diagnosing cardiac amyloidosis. Cardiac scintigraphy, using bone-avid tracers like 99mTc-PYP, 99mTc-DPD, and 99mTc-HMDP, is instrumental in distinguishing between transthyretin amyloidosis and light chain amyloidosis. PET, with tracers such as 11C-Pittsburgh Compound B (11C-PiB) and 18F-Florbetapir, offers significant potential in measuring amyloid burden and monitoring disease progression, providing detailed insights into the myocardial involvement. SUMMARY: The advancements in nuclear imaging techniques significantly impact the management of cardiac amyloidosis. These methods allow for a more accurate diagnosis, detailed assessment of disease extent, and better differentiation between amyloidosis types, which are crucial for tailoring treatment approaches. The integration of these techniques into clinical practice is essential for improving patient outcomes and advancing research in cardiac amyloidosis.

The Emerging Specialty of Cardio-Rheumatology.

PURPOSE OF REVIEW: In this review, we aimed to summarize the different aspects of the field of cardio-rheumatology, the role of the cardio-rheumatologist, and future research in the field. RECENT FINDINGS: Cardio-rheumatology is an emerging subspecialty within cardiology that focuses on addressing the intricate relationship between systemic inflammation and cardiovascular diseases. It involves understanding the cardiovascular impact of immune-mediated inflammatory diseases on the heart and vascular system. A cardio-rheumatologist's role is multifaceted. First, they should understand the cardiac manifestations of rheumatological diseases. They should also be knowledgeable about the different immunotherapies available and side effects. Additionally, they should know how to utilize imaging modalities, either for diagnosis, prognosis, or treatment monitoring. This field is constantly evolving with new research on both treatment and imaging of the effects of inflammation on the cardiovascular system.

Ejection fraction and ventricular volumes on rubidium positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the non-invasive gold standard for non-invasively determining left ventricular volumes (LVVs) and ejection fraction (EF). We aimed to assess the accuracy of LVV and left ventricular ejection fraction measured by positron emission tomography (PET) as compared to CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. Analysis was performed to evaluate the agreement between the raw and body-surface-area-normalized left ventricular volume (LVV) and EF derived from PET vs. those derived from CMR. RESULTS: The study population consisted of 669 patients (mean age 62 ± 13 years, 65% male). The median (interquartile range [IQR]) duration between CMR and PET imaging was 36 (7-118) days. The median (IQR) EF values were 52% (38-63%) on CMR and 53% (37-65%) on PET (mean difference: 0.53% ± 9.1, P = 0.129) with a strong correlation (Spearman rho = 0.84, P < 0.001; Intraclass Correlation Coefficient 0.84, 95% confidence interval [CI]: 0.82-0.86, P < 0.001; Lin's concordance correlation coefficient was 0.844, 95% CI: 0.822 to 0.865). Results were similar with LVV, normalized LVV/EF, and in subgroups of patients with reduced EF, coronary artery disease scar, and LV hypertrophy as well as in patients with defibrillators. However, PET tended to underestimate LVV compared to CMR. CONCLUSION: Our analysis showed a strong correlation of EF and LVV by PET against a reference standard of CMR, whereas PET significantly underestimated LVV, but not EF, compared to CMR.

The utility of beta-hydroxybutyrate in detecting myocardial glucose uptake suppression in patients undergoing inflammatory [18F]-FDG PET studies.

PURPOSE: We evaluated whether serum beta-hydroxybutyrate (BHB) can identify adequate suppression of the left ventricle (LV) among patients undergoing [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET) for cardiac inflammatory/infectious studies. METHODS: Consecutive patients who underwent [18F]-FDG PET imaging were included. Serum BHB levels were measured in all patients on the day of imaging prior to injecting [18F]-FDG. Myocardial [18F]-FDG suppression was defined if [18F]-FDG uptake in the walls of myocardium, measured using standardized uptake values (SUV), was lower than the blood pool. The optimal threshold of BHB to identify myocardial suppression was based on receiver operating characteristics (ROC) in a random 30% sample of the study population (derivation cohort) and tested in the remaining 70% of sample (validation cohort). RESULTS: A total of 256 images from 220 patients were included. Patients with sufficient LV suppression had significantly higher BHB levels compared to those with non-suppressed myocardium (median (IQR) BHB 0.6 (0.3-0.8) vs. 0.2 (0.2-0.3) mmol/l, p < 0.001, respectively). BHB level ≥ 0.335 mmol/l had a sensitivity of 84.90% and a specificity of 92.60% to identify adequate LV suppression in the validation cohort. All patients (100%) with BHB ≥ 0.41 mmol/l had adequate myocardial suppression compared to 29.63% of patients with BHB ≤ 0.20 mmol/l. CONCLUSION: Serum BHB level can be used at the point of care to identify sufficient LV suppression in patients undergoing [18F]-FDG PET cardiac inflammatory/infectious studies. Central illustration (image to the right) shows representative cases of patient images and BHB and, in the image to the left, shows the sensitivity and specificity to identify left myocardial suppression using BHB in validation group.

The Role of Cardiac PET in Diagnosis and Prognosis of Ischemic Heart Disease: Optimal Modality Across Different Patient Populations.

PURPOSE OF REVIEW: Despite single-photon emission computerized tomography (SPECT) being the most used nuclear imaging technique for diagnosis of coronary artery disease (CAD), many now consider positron emission tomography (PET) as a superior modality. This review will focus on the advances of cardiac PET in recent years and its advantages compared to SPECT in diagnosis and prognosis of CAD. RECENT FINDINGS: PET's higher resolution and enhanced diagnostic accuracy, as well as lower radiation exposure, all help explain the rationale for its wider spread and use. PET also allows for measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which aids in several different clinical scenarios, such as diagnosing multivessel disease or identifying non-responders. PET has also been shown to be useful in diagnosing CAD in various specific populations, such as patients with prior COVID-19 infection, cardiac transplant, and other comorbidities.

Incremental prognostic value of positron emission tomography derived left ventricular mass.

BACKGROUND: Left ventricular hypertrophy has been shown to be an independent predictor of outcomes in patients with coronary artery disease (CAD). We aimed to determine the incremental prognostic value of positron emission tomography (PET) derived left ventricular mass (LVM) to clinical variables and myocardial flow reserve (MFR). METHODS: We included consecutive patients who had clinically indicated PET myocardial perfusion imaging for suspected or established CAD. Patients were followed from the date of PET imaging for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention/coronary artery bypass grafting 90 days after imaging). RESULTS: A total of 2357 patients underwent PET MPI during the study period (47% female, mean age 66 ± 12 years, 87% hypertensive, 47% diabetic, 79% dyslipidemia). After a mean follow-up of 11.6 ± 6.6 months, 141 patients (6.0%, 5.1 per 1000 person-year) experienced MACE (86 D/24 MI/39 PCI/9 CABG). In nested multivariable Cox models, LVM was not independently associated with outcomes (HR 1.00, P = .157) and had no incremental prognostic value (C index: 0.75, P = .571) over MFR and clinical variables. CONCLUSION: Our analysis shows that LVM provides no independent and incremental prognostic value over MFR and clinical variables.

Splenic switch-off in regadenoson 82Rb-PET myocardial perfusion imaging: assessment of clinical utility.

BACKGROUND: Splenic switch-off (SSO) is a phenomenon describing a decrease in splenic radiotracer uptake after vasodilatory stress. We aimed to assess the diagnostic utility of regadenoson-induced SSO. METHODS: We included consecutive patients who had clinically indicated Regadenoson Rb-82 PET-MPI for suspected CAD. This derivation cohort (no perfusion defects and myocardial flow reserves (MFR) ≥ 2) was used to calculate the splenic response ratio (SRR). The validation cohort was defined as patients who underwent both PET-MPI studies and invasive coronary angiography (ICA). RESULTS: The derivation cohort (n = 100, 57.4 ± 11.6 years, 77% female) showed a decrease in splenic uptake from rest to stress (79.9 ± 16.8 kBq⋅mL vs 69.1 ± 16.2 kBq⋅mL, P < .001). From the validation cohort (n = 315, 66.3 ± 10.4 years, 67% male), 28% (via SRR = 0.88) and 15% (visually) were classified as splenic non-responders. MFR was lower in non-responders (SRR; 1.55 ± 0.65 vs 1.76 ± 0.78, P = .02 and visually; 1.18 ± 0.33 vs 1.79 ± 0.77, P < .001). Based on ICA, non-responders were more likely to note obstructive epicardial disease with normal PET scans especially in patients with MFR < 1.5 (SRR; 61% vs 34% P = .05 and visually; 68% vs 33%, P = .01). CONCLUSION: Lack of splenic response based on visual or quantitative assessment of SSO may be used to identify an inadequate vasodilatory response.

Cardiovascular magnetic resonance for suspected cardiac amyloidosis: where are we now?

Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality approach making use of echocardiography, cardiac magnetic imaging (CMR), and nuclear imaging. With superior tissue characterization, high-resolution imaging, and precise cardiac assessment, CMR has emerged as a versatile tool in the workup of cardiac amyloidosis with a wide array of parameters both visual and quantitative. This includes late gadolinium enhancement patterns, T1/T2 mapping, and extracellular volume (ECV) measurement providing robust diagnostic accuracies, patient stratification, and prognostication. Recent advancements have introduced new measures able to identify early disease, track disease progression, and response to therapy positioning CMR as an instrumental imaging modality in the era of rising interest in CA screening and emerging effective therapies.

99mTechnetium-labeled cardiac scintigraphy for suspected amyloidosis: a review of current and future directions.

Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality approach making use of echocardiography, cardiac magnetic imaging, and nuclear imaging. Technetium (Tc)-labeled cardiac scintigraphy has witnessed a resurgence in its application for the workup of CA. Advancements in disease-modifying therapies have fueled the rapid adoption of cardiac scintigraphy using bone tracers and the need for transformative novel studies. The goal of this review is to present diagnostic utility, currently recommended protocols, as well as a glimpse into the rapid evolution of Tc-labeled cardiac scintigraphy in the diagnosis of CA.

The utility of positron emission tomography in cardiac amyloidosis.

Cardiac amyloidosis, characterized by progressive restrictive cardiomyopathy, presents unusual diagnostic challenges. Conventional cardiac scintigraphy has shown limited utility in the quantification of disease burden and serial follow-up of cardiac amyloidosis. The advent of specialized positron emission tomography with specific amyloid-binding radiotracers has the potential to change currently employed diagnostic algorithms for the imaging of cardiac amyloidosis. This review aims to discuss the diagnostic utility of amyloid-binding radiotracers, including Pittsburg compound B, florbetapir, florbetapan, and sodium fluoride. These tracers have promising potential for the early detection of the particular type of cardiac amyloidosis, pursuing relevant medical intervention, assessing amyloid burden, monitoring treatment response, and overall prognostication.

Change in positron emission tomography perfusion imaging quality with a data-driven motion correction algorithm.

INTRODUCTION: Cardiac motion frequently reduces the interpretability of PET images. This study utilized a prototype data-driven motion correction (DDMC) algorithm to generate corrected images and compare DDMC images with non-corrected images (NMC) to evaluate image quality and change of perfusion defect size and severity. METHODS: Rest and stress images with NMC and DDMC from 40 consecutive patients with motion were rated by 2 blinded investigators on a 4-point visual ordinal scale (0: minimal motion; 1: mild motion; 2: moderate motion; 3: severe motion/uninterpretable). Motion was also quantified using Dwell Fraction, which is the fraction of time the motion vector shows the heart to be within 6 mm of the corrected position and was derived from listmode data of NMC images. RESULTS: Minimal motion was seen in 15% of patients, while 40%, 30%, and 15% of patients had mild moderate and severe motion, respectively. All corrected images showed an improvement in quality and were interpretable after processing. This was confirmed by a significant correlation (Spearman's correlation coefficient 0.626, P < .001) between machine measurement of motion quantification and physician interpretation. CONCLUSION: The novel DDMC algorithm improved quality of cardiac PET images with motion. Correlation between machine measurement of motion quantification and physician interpretation was significant.

Prognostic value of global myocardial flow reserve in patients with history of coronary artery bypass grafting.

AIMS: It is not well understood whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) is prognostic among patients with prior coronary artery bypass grafting (CABG). METHODS AND RESULTS: Consecutive patients with a clinical indication for PET were enrolled in the Houston Methodist DeBakey Heart and Vascular Center PET registry and followed prospectively for incident outcomes. The primary outcome was a composite of all-cause death, myocardial infarction (MI)/unplanned revascularization, and heart failure admissions. Cox proportional hazards models were used to study the association between MFR (<2 vs. ≥2) and incident events adjusting for clinical and myocardial perfusion imaging variables. The study population consisted of 836 patients with prior CABG; mean (SD) age 68 (10) years, 53% females, 79% Caucasian, 36% non-Hispanic, and 66% with MFR <2. Over a median (interquartile range [IQR]) follow-up time of 12 (4-24) months, there were 122 incident events (46 HF admissions, 28 all-cause deaths, 23 MI, 22 PCI/3 repeat CABG 90 days after imaging). In adjusted analyses, patients with impaired MFR had a higher risk of the primary outcome [hazard ratio (HR) 2.06; 95% CI 1.23-3.44]. Results were significant for admission for heart failure admissions (HR 2.92; 95% CI 1.11-7.67) but not for all-cause death (HR 2.01, 95% CI 0.85-4.79), or MI/UR (HR 1.93, 95% CI 0.92-4.05). CONCLUSION: Among patients with a history of CABG, PET-derived global MFR <2 may identify those with a high risk of subsequent cardiovascular events, especially heart failure, independent of cardiovascular risk factors and perfusion data.

Prognostic value of positron emission tomography derived myocardial flow reserve: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Positron Emission Tomography (PET)-derived myocardial flow reserve (MFR) has been shown to have a role in the diagnosis and prognosis of patients with coronary artery disease (CAD). We performed a systematic review and meta-analysis to summarize the body of literature and synthesize the evidence on the prognostic role of PET-derived MFR in patients with known or suspected CAD. METHODS: A comprehensive literature search of the Medline database from its inception to August 2023, in humans, in any language, was conducted for clinical studies examining the prognostic value of PET imaging in patients of any age, sex, and CAD status. Systematic screening and data extraction of the identified studies were followed by quantitative meta-analysis of PET-MFR's role in predicting adverse clinical events using random effect model. Studies were appraised using the modified Newcastle-Ottawa tool. RESULTS: A total of 21 studies assessing the prognostic role of PET derived MFR in 46,815 patients with known and/or suspected CAD were included (mean (SD) age 66 (4) years, 48% women). The mean follow-up duration was 36 months (range 10-96). Cardiovascular risk factors were prevalent (73% hypertension, 35% diabetes and 67% dyslipidemia). The definition of the composite outcome varied between studies, with various combinations of mortality, non-fatal myocardial infarction, hospitalization, and coronary revascularization. Pooled impaired MFR was significantly associated with an increased risk of adverse outcomes (RR = 2.94, 95% CI 2.42-3.56, p < 0.001). Results were similar in a subgroup of patients with suspected CAD. CONCLUSIONS: The available body of evidence shows that impaired PET-derived MFR measured using different tracers and PET systems is strongly associated with an increased risk of adverse cardiovascular events. Limitations of this review include observational nature of studies, marked heterogeneity in patient populations, inconsistency in thresholds to define abnormal MFR, and differing components for the composite outcome.

Incremental prognostic value of digital positron emission tomography derived myocardial flow reserve: A prospective cohort study.

BACKGROUND: Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. METHODS: Consecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. RESULTS: The final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0-15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0-4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). CONCLUSION: MFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease. METHODS AND RESULTS: Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58-338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection. CONCLUSION: The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.

Prognostic Interplay Between Coronary Artery Calcium Scoring and Cardiorespiratory FItness: The CAC-FIT Study.

OBJECTIVE: To assess the incremental prognostic role of coronary artery calcium score (CACS) and exercise capacity (EC), two independent prognostic tests in the assessment of patients with coronary artery disease. METHODS: The cohort consisted of patients who had clinically indicated exercise stress testing and CACS assessment from January 1, 2015, to September 30, 2021, with a median of 27 days between each other. Exercise capacity was defined by peak metabolic equivalents of task (METs) achieved during exercise stress test. The CACS was determined by the Agatston method. Patients were observed from the latest test date to incident major adverse cardiac events (inclusive of all-cause death, nonfatal myocardial infarction, late revascularization, and admission for heart failure). RESULTS: There were a` total of 1932 patients in the study population (mean age, 56±12 years; 42% female, 48% hypertension, 21% diabetes, 48% dyslipidemia). Peak METs below 6 was achieved in 8% of patients, and the median (interquartile range) CACS was 9 (0-203). In multivariable Cox regression models, both CACS (1 unit increase in log CACS: hazard ratio, 1.19; 95% CI, 1.06 to 1.34; P=.003;) and EC (1 unit increase in peak METs: hazard ratio, 0.89; 95% CI, 0.81 to 0.97; P=.01) were independently associated with outcomes. Using CACS+EC added incremental prognostic value over clinical and fitness models (C index increase from 0.68 to 0.75; P=.015). Incident event rates increased across categories of CACS and EC. CONCLUSION: Our analysis found that CACS and EC have complementary risk-stratifying roles in coronary artery disease.

Interoperator reliability of an on-site machine learning-based prototype to estimate CT angiography-derived fractional flow reserve.

BACKGROUND: Advances in CT and machine learning have enabled on-site non-invasive assessment of fractional flow reserve (FFRCT). PURPOSE: To assess the interoperator and intraoperator variability of coronary CT angiography-derived FFRCT using a machine learning-based postprocessing prototype. MATERIALS AND METHODS: We included 60 symptomatic patients who underwent coronary CT angiography. FFRCT was calculated by two independent operators after training using a machine learning-based on-site prototype. FFRCT was measured 1 cm distal to the coronary plaque or in the middle of the segments if no coronary lesions were present. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate interoperator variability effect in FFRCT estimates. Sensitivity analysis was done by cardiac risk factors, degree of stenosis and image quality. RESULTS: A total of 535 coronary segments in 60 patients were assessed. The overall ICC was 0.986 per patient (95% CI 0.977 to 0.992) and 0.972 per segment (95% CI 0.967 to 0.977). The absolute mean difference in FFRCT estimates was 0.012 per patient (95% CI for limits of agreement: -0.035 to 0.039) and 0.02 per segment (95% CI for limits of agreement: -0.077 to 0.080). Tight limits of agreement were seen on Bland-Altman analysis. Distal segments had greater variability compared with proximal/mid segments (absolute mean difference 0.011 vs 0.025, p<0.001). Results were similar on sensitivity analysis. CONCLUSION: A high degree of interoperator and intraoperator reproducibility can be achieved by on-site machine learning-based FFRCT assessment. Future research is required to evaluate the physiological relevance and prognostic value of FFRCT.

It Takes a Village: Multimodality Imaging of Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is the buildup and infiltration of amyloid plaque in cardiac muscle. An underdiagnosed form of restrictive cardiomyopathy, CA can rapidly progress into heart failure. CA is evaluated using a multimodality approach that includes echocardiography, cardiac magnetic imaging, and nuclear imaging. Echocardiography remains an essential first-line modality that raises suspicion for CA and establishes functional baselines. Cardiac magnetic imaging provides additional incremental value via high-resolution imaging, robust functional assessment, and superior tissue characterization, all of which enable a more comprehensive investigation of CA. Cardiac scintigraphy has eliminated the need for invasive diagnostic approaches and helps differentiate CA subtypes. Positron emission tomography is the first modality introducing targeted amyloid binding tracers that allow for precise burden quantification, early detection, and disease monitoring. In this review, we highlight the role of several cardiac imaging techniques in the evaluation of CA.

Incremental prognostic value of spect over CCTA.

BACKGROUND: Coronary computed tomographic angiography (CCTA) and Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) provide comprehensive anatomic and functional assessment of the coronary arteries useful in the diagnosis and prognosis of patients with coronary artery disease (CAD). We aimed to assess the incremental prognostic role of SPECT physiologic assessment to CCTA in patients with suspected CAD. METHODS: Consecutive patients with suspected CAD undergoing clinically indicated CCTA within 180 days of undergoing SPECT were included. Patients were followed for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention or coronary artery bypass grafting 90-days after imaging test.) RESULTS: The cohort consisted of 956 patients (mean age 61.1 ± 14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive stenosis was found in 14% of patients, while scar (fixed perfusion defect), ischemia and left ventricular ejection fraction <40% were found in 17, 14 and 9% of patients, respectively. In nested multivariable cox regression models, perfusion and left ventricular function when added to a model with CCTA obstructive stenosis significantly improved model risk prediction (Harrell's C = 0.73, p = 0.037) and risk reclassification on a continuous scale (P < 0.001). CONCLUSION: We have shown that a combined assessment of perfusion burden and left ventricular function added incremental value over and above a CCTA based anatomic assessment in patients with suspected CAD.